Tetracycline oral administration

ORAL ADMINISTRATION. To control the infectious process or prevent a bacterial infection, the nurse must keep several important things in mind when administering the tetracyclines, macrolides, and lincosamides. 

Oral administration of bicarbonate may decrease the absorption of ketoconazole. Increased blood levels of quinidine, flecainide, or sympatiiomimetics may occur when these agents are administered with bicarbonate There is an increased risk of crystalluria when bicarbonate is administered with the fluoroquinolones. Fbssible decreased effects of lithium, methotrexate, chlorpropamide, salicylates, and tetracyclines may occur when these drag s are administered with sodium bicarbonate. Sodium bicarbonate is not administered within 2 hours of enteric-coated drugs the protective enteric coating may disintegrate before the drug reaches the intestine. 

Another group of compounds, the tetracyclines, are made by fermentation procedures or by chemical modifications of the natural product. The hydrochloride salts are used most commonly for oral administration and are usually encapsulated because of their bitter taste. Controlled catalytic hydrogenolysis of chlortetracycline, a natural product, selectively removes the 7-chloro atom and produces tetracycline. Doxycycline and minocycline are other important antibacterials. Tetracycline can be prescribed for people allergic to penicillin. Doxycycline prevents traveler s diarrhea. Tetracyclines help many infections including Rocky Mountain spotted fever, Lyme disease, urinary tract infections, bronchitis, amoebic dysentery, and acne. 

Upon oral administration, quinine effectively acts in combination with pyrimethamine, sulfadiazine, and/or tetracycline for treating uncomplicated incidents of chloroquine-resistant forms of P. falciparum. Because of the many associated side effects, its use is extremely limited. Currently, the only indication for use is for forms of malaria that are resistant to other synthetic drugs. Synonyms of this drug are bronchopulmin, nicopriv, quinnam, and others. 

Tetracyclines are a family of antibiotics which display a characteristic 4-fused-core ring structure (Figure 1.16). They exhibit broad antimicrobial activity and induce their effect by inhibiting protein synthesis in sensitive microorganisms. Chlortetracycline was the first member of this family to be discovered (in 1948). Penicillin G and streptomycin were the only antibiotics in use at that time, and chlortetracycline was the first antibiotic employed therapeutically that retained its antimicrobial properties upon oral administration. Since then, a number of additional tetracyclines have been discovered (all produced by various strains of Streptomyces), and a variety of semi-synthetic derivatives have also been prepared (Table 1.18). 

The tetracyclines are distributed throughout body tissues and fluids in concentrations that reflect the lipid solubility of each individual agent. Minocycline and doxycycline are the most lipid soluble, while oxytetracy-chne is the least hpid soluble. The tetracyclines penetrate (but somewhat unpredictably) the uninflamed meninges and cross the placental barrier. Peak serum levels are reached approximately 2 hours after oral administration cerebrospinal fluid (CSF) levels are only one-fourth those of plasma. 

The absorption of tetracycline administered orally is variable and depend upon the type of tetracycline used. The tetracycline form insoluble complexes i.e. chelation with calcium, magnesium, milk and antacids reduce their absorption. Administration of iron also interferes with the absorption of tetracycline. Doxycycline is rapidly and virtually completely absorbed after oral administration and its absorption is not affected by presence of food or milk. 

Tetracyclines mainly differ in their absorption after oral administration and their elimination. Absorption after oral administration is approximately 30% for chlortetracycline 60-70% for tetracycline, oxytetracycline, demeclocycline, and methacycline and 95-100% for doxycycline and minocycline. Tigecycline is poorly absorbed orally and must be administered intravenously. A portion of an orally administered dose of tetracycline remains in the gut lumen, modifies intestinal flora, and is excreted in the feces. Absorption occurs mainly in the upper small intestine and is impaired by food (except doxycycline and... 

In food-producing animals, tetracyclines can be administered orally through feed or drinking water, parenterally, or by intramammary infusion. However, oral administration suppresses initially die ruminal fermentation of plant fiber. The absorption of tetracyclines can be further adversely affected by the presence of metallic ions in the gastrointestinal tract. All tetracyclines have an affinity for metallic ions and should not be administered with milk or high calcium levels in feed unless an upward adjustment in the dosage is made (226-228). 

Doxycycline tends to be more active against some bacteria than other tetracyclines. This is probably due to its slower excretion rather than to enhanced oral absorption. Doxycycline is used in cases where cost is unimportant. It is a very lipophilic drug that shows a high bioavailability, being almost completely absorbed after oral administration to different animal species except chickens (250, 251). 

After oral administration, doxycycline is rapidly and well absorbed from the gastrointestinal tract. It has a half-life of 15-22 h, which is longer than that of other tetracyclines. Following administration by various routes, doxycycline is widely distributed in the body, with highest levels in kidney and liver, besides bones and dentine. Doxycycline may be metabolized for up to 40%, and is largely excreted in feces via bile and intestinal secretion. 

Another subclass of proteases attacks internal peptide bonds and liberates large peptide fragments. Bromelain, a plant protease derived from the stem of the pineapple plant, can even produce detectable serum proteolysis after oral administration (180). Oral therapy with bromelain significandy reduces bruising that stems from obstetrical manipulations (181). Bromelain—pancreatin combinations have been more effective in digestive insufficiency compared to either pancreatin or placebo (182,183). Bromelain may also enhance the activity of antibiotics, especially tetracycline, when administered concurrendy (184). 

Formation of soluble hydrochlorides of basic drugs does not necessarily result in improved bioavailability as was illustrated by comparative absorption studies of tetracyclines and lincomycin and their salts. " " Tetracycline-free bases gave higher plasma levels than their hydrochloride salts, while lincomycin hydrochloride had a lower bioavailability than the hexadecylsulfa-mate salts. These differences have been attributed to a common ion effect with gastric HCl following oral administration. 

Doxycycline and minocycline are more lipophilic tetracyclines. They are well absorbed after oral administration. Their half-lives are 16-18 hours. Their higher affinity for fatty tissues improves their effectiveness and changes their adverse effects profile. Local gastrointestinal irritation and disturbance of the intestinal bacterial flora occur less often than with the more hydrophilic drugs, which have to be given in higher oral doses for sufficient absorption. 

Concomitant oral administration of tetracyclines and iron grossly reduces the absorption of both, because complexes are formed (56,57) there should be an interval of 2-3 hours between the use of the two. 

Tetracycline (chlortetracycline) and oxytetracycline These tetracyclines are incompletely absorbed from the gastrointestinal tract. Plasma concentrations fall with half-lives of 6-12 hours. They are predominantly excreted by the kidney, extrarenal elimination amounting at most to 10-20%. They have a lower affinity for fat and membranes, which means that higher dosages to achieve therapeutic effectiveness. However, higher dosages can contribute to an increased risk of systemic toxic effects and, as absorption from oral administration is incomplete, also to an increased risk of gastrointestinal adverse reactions. 

The tetracyclines are amphoteric antimicrobial agents that can form salts with bases or acids (see Chs 1 and 2). Oxytetracycline is a bitter, yellow, odorless crystalline powder. The base is slightly water soluble and the hydrochloride is readily water soluble and is typically administered to horses by slow i.v. injection. It is effective at 5.5 mg/kg once daily for 2 days or more in the treatment of B. equi but is unlikely to completely clear this infection. It is, therefore, used for premunition. Rapid i.v. injection may cause a precipitous drop in blood pressure and collapse owing to the effects of calcium chelation on the myocardium. Intramuscular injection causes objectionable local reactions in horses and should be avoided. Oral administration may be more... 

Gastrointestinal Ah tetracychnes can produce GI irritation, typically after oral administration. Tolerabihty can be improved by administering the drug with food, but tetracyclines should not be taken with dairy products or antacids. Tetracychne has been associated with esophagitis and pancreatihs. Pseudomembranous colitis caused by overgrowth of C. difficile is a potentially life-threatening complication. 

Various skin reactions rarely may follow the use of any of the tetracyclines. More severe allergic responses are angioedema and anaphylaxis anaphylactoid reactions can occur even with oral administration. Other hypersensitivity reactions are burning of the eyes, cheilosis, glossitis, pruritus ani or vulvae, and vaginitis, which can persist for months after cessation of therapy. Fever, eosinophilia, and asthma also have been observed. Cross-sensitization among the various tetracyclines is common. 

The tetracyclines administered orally or parenterally may lead to the development of superinfections caused by strains of bacteria or fungi resistant to these agents. Pseudomembranous colitis due to overgrowth of toxin-producing C. difficile presents with severe diarrhea, fever, and stools containing mucous membrane neutrophils. Discontinuation of the drug, combined with the oral administration of metronidazole or vancomycin, usually is curative. 

This insolubility not only is inconvenient for the preparation of solutions but also Interferes with blood levels on oral administration. Consequently, the tetracyclines are incompatible with coadministered, multivalent ion-rich antacids and with hematinics, and concomitant consumption of daily products rich in calcium ion also is contraindicated. Further, the bones, of which the teeth are the most visible, are calcium-rich structures at nearly neutral pHs and so accumulate tetracyclines in proportion to the amount and duration... 

Tetracycline is produced by fermentation of Streptomyces aureofaciens and related species or by catalytic reduction of chlortetracycline. The blood levels achieved on oral administration often are irregular. Food and milk lower absorption by approximately 50%. 

It is produced by semisynthesis from other tetracycline molecules and is the most widely used of the tetracycline family. Doxycycline is well absorbed on oral administration (90-100% when fasting reduced by 20% by co-consumption with food or milk), has a half-life permitting once-a-day dosing for mild infections, and is excreted partly in the feces and partly in the urine. 

As tetracyclines have moderate to high lipophilic properties, the poor bioavailability associated with oral administration is somewhat surprising. Papich and Riviere suggest that causes may be multifactorial. As zwitterions, they are mainly ionized at pHs within GIT liquor. Moreover, feed reduces bioavailability, and tetracyclines chelate with polyvalent cations. Oxytetracycline absorption has been shown, experimentally, to be reduced by feed, dairy products, Ca +, Mg +, Al +, and Fe + ions and antacids. Even though doxycycline has a similar structure, affinity for metals is different from that of oxytetracycline with greater affinity for zinc and less for calcium. 

The highest sales in humans and animals were f)-lactams and tetracyclines, respectively. Tetracyclines alone, in veterinary medicine, represented approximately 50.4% of all sales, while tetracyclines, sulfonamides/trimethoprim, P-lactams, and aminoglycosides combined accounted for more than 80% of AMDs used. During the 7-year period, sales of cephalosporins and fluoroquinolones in veterinary medicine increased by 38.4% and 31.6%, respectively. Nevertheless, as percentages of total veterinary sales, their use remained relatively small cephalosporins 0.64% and fluoroquinolones 0.33% in 2005. In animals, oral administration accounted for 88% of sales, and estimated sales for parenteral products were 10.5%. Moreover, while 92% of total tonnage was intended for food-producing animals, 64% of cephalosporins were intended for pets. 

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